Human PAF complexes in endocrine tumors and pancreatic cancer

Abstract

The human RNA polymerase II-associated factor (hPAF) complex is comprised of five subunits that include hPaf1, parafibromin, hLeo1, hCtr9 and hSki8. This multifaceted complex was first identified in yeast (yPAF) and subsequently in Drosophila and humans. Recent advances in the study on hPAF have revealed various functions of the complex in humans that are similar to yPAF, including efficient transcription elongation, mRNA quality control and cell cycle regulation. A major component of the hPAF complex, hPaf1, is amplified and overexpressed in pancreatic cancer. The parafibromin subunit of the hPAF complex is a product of the hereditary hyperparathyroidism type 2 (HRPT-2) tumor-suppressor gene, which is mutated in the germ line of hyperparathyroidism–jaw tumor patients. This review evaluates the role of the hPAF complex and its individual subunits in endocrine and pancreatic cancers. It focuses on the functions of the hPAF complex and its individual subunits and dysregulation of the complex, thus providing an insight into its potential involvement in the development of endocrine cancers and other tumor types.

Keywords::

• endocrine tumor
• hPaf1
• oncogene
• PAF complex
• transcription
• tumor-suppressor gene
• wnt signaling

Financial & competing interests disclosure

The authors on this review article were supported by grants from the National Institutes of Health (RO1 CA78590 and EDRN U01CA111294) and the Department of Defense (PC040502 and OC04110). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. The authors thank Kristi LW Berger (Eppley Institute) for editorial assistance.